title: The MEK5/ERK5 pathway mediates fluid shear stress promoted osteoblast differentiation.
abstract: The aim of this study was to determine the role of the mitogen-activated protein kinase kinase (MEK) 5/extracellular signal-regulated kinase (ERK) 5 pathway in osteoblast differentiation promoted by intermittent fluid shear stress (FSS). MC3T3-E1 osteoblastic cells were subjected to 12 dyn/cm(2) intermittent FSS, and the phenotypic markers for osteoblast differentiation, such as alkaline phosphatase (ALP) activity and expression of osteopontin (OPN) and osteocalcin (OCN), were then examined. The results showed that intermittent FSS could stimulate ERK5 phosphorylation, ALP activity and the expression of OPN and OCN. When the MEK5/ERK5 pathway was selectively inhibited by BIX02189, ALP activity was suppressed, and the expression of OPN and OCN was downregulated. Intermittent FSS induce the expression of Runt-related transcription factor-2 (Runx-2), which is involved in osteoblast differentiation by promoting the transcription of the above genes. Furthermore, the expression of Runx-2 was also reduced after treatment with BIX02189. Finally, we found that intermittent FSS was a more intense stimulus than steady FSS for promoting osteoblast differentiation. In summary, our results suggest that the MEK5/ERK5 pathway mediates osteoblast differentiation promoted by intermittent FSS, which was more effective than steady FSS in the differentiation process. The MEK5/ERK5 pathway also mediates FSS-induced Runx-2 expression in osteoblast differentiation.
authors.affiliation: The Second Clinical Medical College of Lanzhou University , Lanzhou, Gansu Province , P.R. China .
authors.forename: Liang-gong
authors.initials: LG
authors.lastname: Zhao
authors.forename: Shao-long
authors.initials: SL
authors.lastname: Chen
authors.forename: Yuan-jun
authors.initials: YJ
authors.lastname: Teng
authors.forename: Li-ping
authors.initials: LP
authors.lastname: An
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jing-lin
authors.initials: JL
authors.lastname: Ma
authors.forename: Ya-yi
authors.initials: YY
authors.lastname: Xia
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology; D048671:MAP Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology*; D033081:Shear Strength; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D000943:Antigens, Differentiation; D048054:Mitogen-Activated Protein Kinase 7; D048671:MAP Kinase Kinase 5; C578399:Map2k5 protein, mouse